Communications, engagement, and dissemination strategies for the HEALthy Brain and Child Development (HBCD) Study.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Study success depends on the engagement and inclusion of diverse populations of pregnant participants and their children across the United States, including those at high and low risk for prenatal substance use. The Communications, Engagement, and Dissemination (CED) Committee is responsible for the development and implementation of a strategy to promote awareness about the study, encourage participation, and engage HBCD families, community partners, and collaborators.

The HEALthy Brain and Child Development Study (HBCD): NIH collaboration to understand the impacts of prenatal and early life experiences on brain development.

The human brain undergoes rapid development during the first years of life. Beginning in utero, a wide array of biological, social, and environmental factors can have lasting impacts on brain structure and function. To understand how prenatal and early life experiences alter neurodevelopmental trajectories and shape health outcomes, several NIH Institutes, Centers, and Offices collaborated to support and launch the HEALthy Brain and Child Development (HBCD) Study.

Cannabinoid CB1 Receptors Are Expressed in a Subset of Dopamine Neurons and Underlie Cannabinoid-Induced Aversion, Hypoactivity, and Anxiolytic Effects in Mice.

Cannabinoids modulate dopamine (DA) transmission and DA-related behavior, which has been thought to be mediated initially by activation of cannabinoid CB1 receptors (CB1Rs) on GABA neurons. However, there is no behavioral evidence supporting it. In contrast, here we report that CB1Rs are also expressed in a subset of DA neurons and functionally underlie cannabinoid action in male and female mice.

Identification of the Risk Genes Associated With Vulnerability to Addiction: Major Findings From Transgenic Animals.

Understanding risk factors for substance use disorders (SUD) can facilitate medication development for SUD treatment. While a rich literature exists discussing environmental factors that influence SUD, fewer articles have focused on genetic factors that convey vulnerability to drug use. Methods to identify SUD risk genes include Genome-Wide Association Studies (GWAS) and transgenic approaches.

Involvement of the ghrelin system in the maintenance of oxycodone self-administration: converging evidence from endocrine, pharmacologic and transgenic approaches.

Ghrelin, an orexigenic hormone, has emerged as a critical biological substrate implicated in drug reward. However, the response of the ghrelin system to opioid-motivated behaviors and the role of ghrelin in oxycodone self-administration remain to be studied. Here, we investigated the reciprocal interactions between the endogenous ghrelin system and oxycodone self-administration behaviors in rats and the role of the ghrelin system in brain stimulation reward (BSR) driven by optogenetic stimulation of midbrain reward circuits in mice.

Dopamine, behavior, and addiction.

Addictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance.

Synaptic Zn potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior.

Cocaine binds to the dopamine (DA) transporter (DAT) to regulate cocaine reward and seeking behavior. Zinc (Zn) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that Zn concentrations in postmortem brain (caudate) tissue from humans who died of cocaine overdose were significantly lower than in control subjects.

Reconceptualizing non-pharmacologic approaches to Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS): A theoretical and evidence-based approach.

Discussions about non-pharmacologic interventions for Neonatal Abstinence Syndrome and Neonatal Opioid Withdrawal Syndrome (NAS/NOWS) have been minor compared with wider attention to pharmacologic treatments. Although historically under-recognized, non-pharmacologic interventions are of paramount importance for all substance-exposed infants and remain as a first line therapy for the care of infants affected by NAS. Here we examine the role of non-pharmacologic interventions for NAS/NOWS by incorporating theoretical perspectives from different disciplines that inform the importance of individualized assessment of the mother-caregiver/infant dyad and interventions that involve both individuals.

Optogenetic brain-stimulation reward: A new procedure to re-evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter-Cre mice.

Despite extensive research, the rewarding effects of cannabinoids are still debated. Here, we used a newly established animal procedure called optogenetic intracranial self-stimulation (ICSS) (oICSS) to re-examine the abuse potential of cannabinoids in mice. A specific adeno-associated viral vector carrying a channelrhodopsin gene was microinjected into the ventral tegmental area (VTA) to express light-sensitive channelrhodopsin in dopamine (DA) neurons of transgenic dopamine transporter (DAT)-Cre mice.

Definitions of neonatal abstinence syndrome in clinical studies of mothers and infants: an expert literature review.

Neonatal abstinence syndrome (NAS) results from discontinuation of in utero exposures to opioids/substances. The rising incidence of NAS has prompted an increased need for accurate research and public health data. To examine how NAS has been defined in clinical studies of opioid-exposed mothers and infants, a review process was developed based on the RAND/UCLA Appropriateness Method, yielding 888 abstracts.

New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders.

The abuse of illicit psychostimulants such as cocaine and methamphetamine continues to pose significant health and societal challenges. Despite considerable efforts to develop medications to treat psychostimulant use disorders, none have proven effective, leaving an underserved patient population and unanswered questions about what mechanism(s) of action should be targeted for developing pharmacotherapies. As both cocaine and methamphetamine rapidly increase dopamine (DA) levels in mesolimbic brain regions, leading to euphoria that in some can lead to addiction, targets in which this increased dopaminergic tone may be mitigated have been explored.

Introduction to the Special Issue on "Informing Longitudinal Studies on the Effects of Maternal Stress and Substance Use on Child Development: Planning for the HEALthy Brain and Child Development (HBCD) Study".

The HEALthy Brain and Child Development (HBCD) study will establish a large cohort of pregnant women from regions of the country significantly affected by the opioid crisis and follow them and their children for at least 10 years. Findings from this cohort will help researchers understand normative childhood brain development as well as the long-term impact of prenatal and postnatal opioid and other drug and environmental exposures. The study will collect data on pregnancy and fetal development; infant and early childhood structural and functional brain imaging; anthropometrics; medical history; family history; biospecimens; and social, emotional, and cognitive development.

Dissecting the Role of GABA Neurons in the VTA SNr in Opioid Reward.

Opioid reward has traditionally been thought to be mediated by GABA-induced disinhibition of dopamine (DA) neurons in the VTA. However, direct behavioral evidence supporting this hypothesis is still lacking. In this study, we found that the μ opioid receptor (MOR) gene, , is highly expressed in GABA neurons, with ∼50% of GABA neurons in the substantia nigra pars reticulata (SNr), ∼30% in the VTA, and ∼70% in the tail of the VTA (also called the rostromedial tegmental nucleus) in male rats.

Correction: ACNP efforts toward reducing climate change.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

(±)VK4-40, a novel dopamine D receptor partial agonist, attenuates cocaine reward and relapse in rodents.

Background And Purpose: Despite widespread abuse of cocaine, there are no approved treatments for cocaine use disorder. Chronic cocaine use is associated with up-regulated dopamine D receptor expression in the brain. Therefore, most D -based medication development has focused on D antagonists.

Xie2-64, a novel CB receptor inverse agonist, reduces cocaine abuse-related behaviors in rodents.

Cocaine abuse remains a public health threat around the world. There are no pharmacological treatments approved for cocaine use disorder. Cannabis has received growing attention as a treatment for many conditions, including addiction.

Modafinil potentiates cocaine self-administration by a dopamine-independent mechanism: possible involvement of gap junctions.

Modafinil and methylphenidate are medications that inhibit the neuronal reuptake of dopamine, a mechanism shared with cocaine. Their use as "smart drugs" by healthy subjects poses health concerns and requires investigation. We show that methylphenidate, but not modafinil, maintained intravenous self-administration in Sprague-Dawley rats similar to cocaine.

Newly Developed Dopamine D Receptor Antagonists, -VK4-40 and -VK4-116, Do Not Potentiate Cardiovascular Effects of Cocaine or Oxycodone in Rats.

Opioid and cocaine abuse are major public health burdens. Existing medications for opioid use disorder are limited by abuse liability and side effects, whereas no treatments are currently approved in the United States for cocaine use disorder. Dopamine D receptor (DR) antagonists have shown promise in attenuating opioid and cocaine reward and mitigating relapse in preclinical models.